McDowell E M, Nagle R B, Zalme R C, McNeil J S, Flamenbaum W, Trump B F
Virchows Arch B Cell Pathol. 1976 Nov 24;22(3):173-96. doi: 10.1007/BF02889215.
Acute renal failure was induced in male rats by the subcutaneous injection of 4 mg HgC12 per kg body weight. Changes in the proximal tubule were studied by light and electron microscopy at six time intervals from 15 min to 24 h. Renal function was monitored at 6 and 24 h. Between 15 min and 3 h changes were similar in all regions of the proximal tubule (pars convoluta and pars recta). Dispersion of cytoplasmic polysome groups was widespread and mitochondrial matrices were condensed in some cells. No changes were noted in the brush border but increased endocytotic activity occurred in some convoluted tubules at 1 and 3 h. At 6 h severe changes had occurred in the pars recta in the medullary rays. Microvilli of the brush border were focally absent, the mitochondria were swollen and the endoplasmic reticulum was dilated. At this time only subtle changes occurred in the pars recta in the outer stripe of the outer medulla. However by 24 h necrosis was widespread throughout the pars recta, yet changes in the proximal convoluted portion were minimal. A significant azotemia, decreased GFR and increased FENa+ and FEK+ occurred at 6 and 24 h after HgC12 injection. Thus HgC12 at 4 mg per kg body weight produced reproducible renal failure and necrosis involving the pars recta of every nephron but necrosis did not begin in the pars recta until after 6 h while acute renal failure was probably initiated much earlier. The following hypothesis is presented. HgC12 initially interacts with the entire proximal tubule. Although injury is sublethal in the pars convoluta it is responsible for greatly diminished sodium reabsorption and is related to the pathogenesis of the renal failure through feedback mechanisms involving the macula densa and release of renin. This results in renal hemodynamic alterations, decreased GFR and other functional disturbances associated with renal failure. The development of necrosis in the pars recta appears to be a relatively late event, possibly due to further accumulation of Hg++ in this region. In any case, the necrosis appears pathogenetically dissociable from the mechanism of acute renal failure.
通过皮下注射每千克体重4毫克氯化汞，在雄性大鼠中诱导急性肾衰竭。在从15分钟到24小时的六个时间间隔，通过光学显微镜和电子显微镜研究近端小管的变化。在6小时和24小时监测肾功能。在15分钟到3小时之间，近端小管的所有区域（曲部和直部）变化相似。细胞质多核糖体群分散广泛，一些细胞中的线粒体基质浓缩。刷状缘未观察到变化，但在1小时和3小时时，一些曲小管的内吞活性增加。在6小时时，髓放线中的直部发生了严重变化。刷状缘的微绒毛局部缺失，线粒体肿胀，内质网扩张。此时，外髓质外带的直部仅发生细微变化。然而到24小时时，整个直部广泛发生坏死，但近端曲部的变化最小。在注射氯化汞后6小时和24小时出现显著的氮质血症、肾小球滤过率降低以及滤过钠分数（FENa +）和滤过钾分数（FEK +）增加。因此，每千克体重4毫克的氯化汞产生了可重复的肾衰竭和坏死，累及每个肾单位的直部，但直部的坏死直到6小时后才开始，而急性肾衰竭可能更早开始。提出了以下假设。氯化汞最初与整个近端小管相互作用。尽管在曲部损伤是亚致死性的，但它导致钠重吸收大大减少，并通过涉及致密斑和肾素释放的反馈机制与肾衰竭的发病机制相关。这导致肾血流动力学改变、肾小球滤过率降低以及与肾衰竭相关的其他功能障碍。直部坏死的发生似乎是一个相对较晚的事件，可能是由于该区域汞离子的进一步积累。无论如何，坏死在发病机制上似乎与急性肾衰竭的机制可分离。
